Review of the essentials of computational Biochemistry; importance and implications. (Page 1)

Contents

• Introduction to DNA molecule
• Importance of gene and chromosome in protein synthesis
• DNA sequence and mRNA
• Introns and Exons
• cDNA
• Polymorphism
• Genetic Disease

Introduction to DNA molecules

The major Biomolecule studied in computational Biochemistry are the DNA and protein. A lot of work has been done to unravel the mysteries of transfer of genetic information from parents to offspring through the DNA and the machineries through which this takes place, which also is the ultimate product of DNA metabolism (the protein). Effective discussion of protein cannot be made without making mention of DNA from which it is derived.

The DNA is an organic macromolecule made up of deoxyribose sugar and phosphate backbone, with a cross linking arm of a nitrogenous base which can either be purine or pyrimidine. They are usually found in the body in a duplex intertwined state, which actually consist of two complimentary strands of DNA.

The important part of DNA that decides the kind of information it carries is the Nitrogenous base arm . The pairing of the double stranded DNA follows a particular pattern. There are four major nitrogenous bases that can be found in the human DNA; Adenine, (A) Guanine, (G) Cytosine (C) and thymine (T). The two purine bases A and G complementarily pairs with the two pyrimidine bases, thymine and cytosine respectively with a double and triple bond respectively to give a double stranded DNA.

Importance of gene and chromosome in protein synthesis back to top

On the course of protein synthesis, the exact sequence and type of nitrogenous base in each single stranded DNA are preserved during the replication and transcription processes.

A genetically normal human has 46 set of chromosome, which they inherit from their parents. Each chromosome actually is a long single stranded DNA that is extensively super coiled with each other. Each chromosome is divided into hundreds of different section of DNA sequences that codes for different unique proteins. Each of these sectional divisions of DNA sequences is referred to as genes.

Each gene occupies a specific position in a chromosome in all organisms of the same species. For example in all human, the gene that codes for Elastase 2 neutrophil is found in chromosome number 19 and spans through position 803,291-807,246 of the DNA sequence for that chromosome.

The knowledge of the gene location of any particular gene or protein is very important for research studies that involve gene extraction or transgenic and genetic engineering studies.

DNA sequence and mRNA back to top

DNA sequence actually refers to the sequence of the nitrogenous base on a single DNA strand. It is conventionally named or listed in a 51 31 direction. (51 and 31 refers to the position of phosphates attained to the sugar ring) this sequence is different from mRNA, cDNA and coding DNA.

DNA sequence contains the raw and unedited sequence of the nitrogenous bases present in the chromosome. Before a gene is used to manufacture any protein, the information of the gene present in the chromosome is transcribed to a messenger RNA. (mRNA)

The mRNA belongs to a group of nucleic acid that contains a ribose sugar instead of a deoxyribose sugar as found in the DNA. The mRNA sequence differs from the DNA sequence in that it contains Uracil instead of thymine as found in DNA. The transcription of the information on the segment of chromosomal DNA of interest, to a mRNA before protein synthesis commences, is to preserve the integrity of the chromosomal DNA (coding DNA).

Introns and Exons back to top

The newly synthesized mRNA strand contains the introns and the exons. The introns are those segments of the DNA sequence that does not code for any amino acid. Exons are the segments of the DNA sequence that codes for amino acid. The newly transcribed mRNA is edited during which the introns are spliced off and the exons are joined together. Some other signaling sequences are added before and/or behind the edited mRNA

cDNA back to top

CDNA is a complimentary DNA obtained from the action of reverse transcriptase on mRNA. It is usually obtained by cloning mRNA in bacteria cells and subsequently purifying and sequencing the resultant DNA. The sequence of the cDNA is an exact complement of the mRNA from which it was synthesized.

Every three-nucleotide codes for one amino acid. Each unit of the triple coding nucleotide sequence is referred to as a codon. The usual starting codon is AUG which codes for methionine, while the usual stop codons are UGA, UAA, UAG and they don’t code for any amino acid.

The mode of representing the nucleotide sequences (cDNA, coding etc) in bioinformatic sites is their mRNA equivalent but differs in the content of the sequence. Also thymine is used in place of Uracil in both mRNA, cDNA and DNA sequence so essentially the starting codon is represented as ATG while the stop codon are TGA, TAA or TAG. Some site contains tools that can be used to reverse any particular sequence.

Polymorphism back to top

No two individual have exactly the same set of DNA sequence. Variation exists. These variations that exists between different individual’s genomic constituents is referred to as polymorphism. Some regions of the human genomic sequence are more variable than others. The more constant part of the sequence are very similar in a larger percentage of the population.

In some rare cases, one nucleotide or nitrogenous base may differ from that of the larger population, such difference in one nucleotide is referred to as a Single Nucleotide Polymorphism (SNP). Some times these SNPs may result to some forms of genetic disease while in some cases, it may be “silent”.

Usually when there is a SNP, the different nucleotide, will alter the codon sequence, which will also affect the type of amino acid that is encoded by the codon. The alteration in the amino acid will also cause an alteration in the final three-dimensional structure and function of the protein.

Genetic Disease back to top

Genetic diseases usually result from the malfunction or the non-functionality of one or more protein in the body. It could either be caused by environmental or congenital factors. Its occurrence can always be traced back to the gene from which the proteins were produced.
In most cases, polymorphic genes usually result in genetic disorders. Some cases of genetic disorders may results from environmental factors, such as the damage to DNA, as a result of exposure to mutagens.

Since faulty genes are the main cause of genetic disorders, its treatment also requires that the faulty gene is located and subjected to different genetic therapeutic techniques such as gene replacement therapies. Such work requires extensive knowledge of computational biochemistry.